A PILOT-STUDY OF DEXTROMETHORPHAN IN NALOXONE-PRECIPITATED OPIATE WITHDRAWAL

Dextromethorphan and its metabolite dextrorphan antagonize N-methyl-D- aspartate (NMDA)-mediated activity in pre-clinical studies. We examine d dextromethorphan's effects on naloxone-precipitated opiate withdrawa l in opiate-dependent subjects stabilized on 25 mg of methadone. Subje cts received challenges on three different days with 0.4 mg of intramu scular naloxone. Pretreatment 1 h before naloxone was with dextrometho rphan in a double-blind, balanced, randomized design with either place bo, dextromethorphan 60 mg, or dextromethorphan 120 mg for six subject s; and placebo, dextromethorphan 120 mg, or dextromethorphan 240 mg fo r five subjects. There was considerable inter-individual variability i n the response to dextromethorphan, but no net attenuation by dextrome thorphan on any withdrawal measure assessed. Two of three subjects det oxified from methadone with dextromethorphan 60 mg orally every 4 h de monstrated considerable withdrawal.